Parenteral control of gastric acid hypersecretion in ZES patients is neccessary perioperatively or when oral medications cannot be taken for other reasons (e.g. during chemotherapy). IV histamine H2-receptor antagonists (H2RA) are able to control AO but very high doses of continuously infused agents are required. In the current study we evaluated the efficacy and safety of 15 min IV infusions of the proton pump inhibitor, PANTO (80-120 mg, q8h-q12h) in controlling AO for up to 7 days in 10 ZES patients (mean age 52.8 yrs [range 32-64], disease duration 6.9 yrs [range 1-16]). Effective control was defined as an AO <10 mEq/h (<5 mEq/h in patients with prior acid-reducing surgery). 4 patients were male, 3 had MEN-1 syndrome, 2 had prior acid-reducing surgery (both Whipple's operations), 1 had previously received chemotherapy and 5 (including the 2 with Whipple's operations) had undergone gastrinoma resections but none were cured. Prior to the study, AO was managed with oral PPIs in all patients (9 with omeprazole [20 mg QD to 60 mg BID] and one with lansoprazole [30 mg BID]). Mean (+/- SEM) prestudy basal acid output (BAO) in the absence of other PPIs for 7 days and H2RAs for 30 hrs was 37.8+6.9 mEq/h (range 15.2-84.5). Following an initial IV dose of 80 mg of PANTO, AO was controlled within the first hr in all patients. Mean AO 24 and 48 hours after the first IV PANTO dose was 3.6 +/- 1.1 and 2.6 +/- 2.8 mEq/h, respectively. A dose of 80 mg q12h was effective in 7/10 patients (70%) for up to seven days. 3 patients required upward dose titration. AO increased above the control value in the 9th hr after the first dose in 1 patient (a sporadic ZES male with a prior gastrinoma resection) and the dose was increased to 120 mg q12h with effective control thereafter. AO increased above the control value within 3 hrs in two patients (an MEN-1 syndrome male and a sporadic ZES female, neither with prior gastrinoma surgery). The dose was increased to 80 mg q8h with effective control in both patients within 24 hrs of dose escalation. At offset, AO remained controlled for 6 hours beyond the next expected dose in 8 patients. Breakthrough occured in the remaining 2 patients (BAO 47.9 and 48.3) after 3 and 5 hrs, respectively. No adverse events were noted. Thus, 160 mg of IV PANTO given in 2 divided doses controlled AO for up to 7 days in 70% of ZES patients. A higher daily divided dose of 240 mg IV controlled AO in all patients. IV PANTO provides significant advantages over existing methods for rapid and effective control of AO in ZES patients who cannot take oral agents.